PREPARATION AND USE IN AMINO-ACID SYNTHESIS OF A NEW CHIRAL GLYCINE DERIVATIVE - (R)-TERT-BUTYL AND (S)-TERT-BUTYL BUTYL-4-METHOXY-2,5-DIHYDROIMIDAZOLE-1-CARBOXYLATE (BDI)

The title compound BDI is prepared on multigram scale, either by resol ution of the precursor 2-tert-butylimidazolidin-4-one (from glycine am ide and pivalaldehyde) through diastereomeric salts (Scheme 2) or by p reparative chromatographic enantiomer separation on a chiral column. L ithiated BDI derivatives are highly nucleophilic species, combining th e structural elements of a Li enaminate, of an enolether and of an N-B oc-enaminate (E, G). They react with complete diastereoselectivity (NM R analysis) from the face trans to the tert-butyl group. The electroph iles employed are primary and secondary alkyl, allyl, benzyl, and prop argyl halides (Schemes 3 and 5), enoates (in Michael additions, Scheme 7), as well as aliphatic and aromatic aldehydes (in aldol additions, Scheme 8), When a third, exocyclic, stereocenter is formed in these re actions, there is a high degree of enantiomer differentiation (with ra c. sec. halides, products 10-12) and of enantiotopic face differentiat ion (with enoates and aldehydes, products 40-50). The reactions are so clean that highly efficient in-situ double alkylations are feasible, in which the sequence of addition of the two different electrophiles d etermines the configuration at the newly formed stereogenic center (Sc heme 5), In contrast to derivatives of previously reported chiral glyc ine reagents, the products from BDI are converted to methyl esters of amino acids under mild conditions and without concomitant formation (. .. and the need for recovery or removal) of a chiral auxiliary; the me thod is compatible with acid-sensitive side chains in the alpha-amino acids and alpha-branched alpha-amino acids to be synthesized (Schemes 4 and 6). The addition of Li-BDI to aldehydes furnishes, after hydroly sis, alpha-amino-beta-hydroxy acids of erythro configuration (allo-thr eonine analogs, Scheme 8); a model for the stereochemical course of th is reaction (rel. topicity unlike) is proposed, and compared with the corresponding conversions of analogous oxazolidinone and imidazolidino ne Li enolates which occur with rel. topicity like.